The major protein component in the serum of the developing mammalian fetus is alpha fetoprotein (AFP), which is synthesized in the embryonic liver and yolk sac. After birth the rate of synthesis of AFP in liver decreases drastically to levels which are barely detectable in non-pregnant adults. Synthesis of AFP is resumed in adult liver during liver regeneration, and in specific tumors such as hepatomas and teratocarcinomas. In contrast, serum albumin, which is the major serum protein synthesized by the adult liver, increases from low levels early in development, to high, relatively constant levels after birth and in adult life. These serum proteins most probably arose in evolution as the consequence of a gene duplication, a conclusion based on a striking similarity in the organization of the coding segments of their genes in the mouse genome, and a 50% conservation of sequence homology in primary sequences. This grant proposes to examine, by DNA sequencing, the detailed structure of the coding intervening and flanking sequences in these genes in order to elucidate the extent of their divergence and to examine the presence of a thrice-repeated domain within each gene. The chromosomal location of the AFP gene will be determined using somatic cell hybrids between mouse and hamster cells. The synthesis and turnover of AFP and albumin mRNAs in teratocarcinoma cells and fetal liver will be studied, to assess the contributions of transcriptional and post-transcriptional modulation in their regulation. The DNA sequences required for accurate transcription in vitro and in vivo, using DNA-mediated gene transfer, will be identified.